Study on inhibition of cytochrome P-450-dependent mixed function oxidation by ethanol
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- HAYASHI Norio
- First Department of Medicine, Osaka University Medical School
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- SATO Nobuhiro
- First Department of Medicine, Osaka University Medical School
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- KASAHARA Akinori
- First Department of Medicine, Osaka University Medical School
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- KISHIDA Takashi
- First Department of Medicine, Osaka University Medical School
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- MEREN Haruya
- First Department of Medicine, Osaka University Medical School
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- FUSAMOTO Hideyuki
- First Department of Medicine, Osaka University Medical School
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- KAMADA Takenobu
- First Department of Medicine, Osaka University Medical School
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- ABE Hiroshi
- First Department of Medicine, Osaka University Medical School
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- PETERSON Julian A.
- University of Texas, Southwestern Medical School
Bibliographic Information
- Other Title
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- エタノールによるチトクロームP‐450依存性薬物水酸化反応抑制メカニズムに関する検討
- エタノール ニヨル チトクローム P 450 イゾンセイ ヤクブツ スイサンカ
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Abstract
The cytochrome P-450 in liver microsome catalyzes the drug oxidation by using oxygen and NADPH. We have investigated the mechanism on the inhibition of cytochrome P-450-dependent mixed function oxidation by ethanol.<BR>NADPH oxidation decreased with increasing ethanol concentration in liver microsomes. Ethanol induced a reverse type I binding spectrum, and competitively inhibited the binding of hexobarbital to liver microsome due to the displacement of the endogeneous substrate.<BR>The NADPH-dependent reduction of liver microsomal cytochrome P-450 was biphasic and composed of two concurrent first-order reactions. The addition of hexobarbital increased the both rate constant for the fast and slow phase. The rate constant for the fast phase was decreased by the addition of ethanol, but the rate constant for the slow phase remained unchanged. Therefore, the inhibition of mixed function oxidation by ethanol may be due partly to the decrease of NADPH-cytochrome P-450 reductase activity resulting from the decrease of substrates bound to cytochrome P-450 by ethanol.
Journal
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- Kanzo
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Kanzo 23 (2), 109-115, 1982
The Japan Society of Hepatology
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Keywords
Details 詳細情報について
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- CRID
- 1390282679767292800
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- NII Article ID
- 130000878170
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- NII Book ID
- AN00047770
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- ISSN
- 18813593
- 04514203
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- NDL BIB ID
- 2482290
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed